RESUMEN
INTRODUCTION: Lyme borreliosis, caused by Borrelia burgdorferi sensu stricto in the United States and by several Borrelia species in Europe and Asia, has a great impact on the health of the global population. There are human vaccines available, such as the outer surface protein A (OspA) vaccine, but still more evidence is needed to verify its function. We investigated the safety, immunogenicity, and efficacy of adjuvanted or non-adjuvanted vaccines containing protective epitopes from Borrelia species OspA serotypes in healthy adults. METHODOLOGY: Seven electronic databases were searched for clinical trials involving vaccine of OspA, with outcome data on safety, immunogenicity, and efficacy. The meta-analysis method was used to compare all vaccination strategies at the same time. RESULTS: Three relevant studies were identified. All were randomized controlled trials (RCTs) or quasi-RCTs. Meta-analysis shows that, compared with low dose, high dose comes with a higher IgG titer with overall effect size of 6.39. For the 30 µg dose, the geometric mean titer was 6918.31, which is statistically significant when compared with 0. With respect to safety, only soreness showed a relatively high incidence of 40% (p < 0.05 when compared with 0, while the other side effects were no difference compared with 0). CONCLUSIONS: The OspA vaccine against Lyme disease is safe and its immunogenicity and efficacy have been verified. Instead of stagnating or giving up, further research on improving the vaccine is needed. On the foundation of preliminary studies, we can attempt to develop new vaccines for human use.
Asunto(s)
Antígenos de Superficie/efectos adversos , Antígenos de Superficie/inmunología , Proteínas de la Membrana Bacteriana Externa/efectos adversos , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/efectos adversos , Vacunas Bacterianas/inmunología , Borrelia burgdorferi/inmunología , Lipoproteínas/efectos adversos , Lipoproteínas/inmunología , Enfermedad de Lyme/prevención & control , Adyuvantes Inmunológicos/administración & dosificación , Anticuerpos Antibacterianos/sangre , Antígenos de Superficie/administración & dosificación , Proteínas de la Membrana Bacteriana Externa/administración & dosificación , Vacunas Bacterianas/administración & dosificación , Ensayos Clínicos como Asunto , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Salud Global , Humanos , Inmunoglobulina G/sangre , Lipoproteínas/administración & dosificación , Dolor/inducido químicamente , Dolor/epidemiología , Resultado del TratamientoRESUMEN
Open-label, multicenter, randomized study (NCT00289913) evaluated immunogenicity, safety, and tolerability of Vaqta (hepatitis A vaccine) administered with PedvaxHIB (Haemophilus b conjugate vaccine [Meningococcal protein conjugate]) & Infanrix (diphtheria/tetanus/acellular pertussis vaccine) in healthy, 15-month-old children. Five groups were evaluated: Group 1 received Vaqta/Infanrix PedvaxHIB on Day-1 and Vaqta at Week-24; Group 2 received Infanrix PedvaxHIB on Day-1, Vaqta at Week-4, and Vaqta at Week-28; Group 3 received Vaqta/PedvaxHIB on Day-1 and Vaqta Week-24; Group 4 received PedvaxHIB on Day-1, Vaqta at Week-4, and Vaqta at Week-28; and Group 5 (safety only) received Vaqta on Day-1 and Vaqta at Week-24. Hepatitis A seropositivity rate (SPR: ≥10 mIU/mL), Hib capsular polyribosylribitol phosphate (PRP) antibody response (>1.0 µg/mL), and geometric mean titers (GMT) to pertussis toxin (PT), pertussis filamentous hemagglutinin antibody (FHA), and pertactin were examined. Non-inferiority statistical criteria required a difference >10% in Hepatitis A SPR, PRP >1.0 µg/mL, and a GMT ratio of >0.67 for pertussis antigens. Injection-site and systemic adverse events (AEs) and daily temperatures were collected. Hepatitis A SPRs were 100% for Groups 1-4, regardless of initial serostatus. Anti-PRP titers were comparable (98.1% - 97.0%) for Groups 1-4. GMT and mean fold-rise were comparable for all 3 pertussis antigen components between concomitant and nonconcomitant groups. Criteria for non-inferiority of immune responses for concomitant vs nonconcomitant administration were met for Hepatitis A, Hib, and pertussis antigens. No statistically significant incidence differences of individual AEs were found between concomitant and nonconcomitant groups. No serious vaccine-related AEs or deaths were reported; no subject discontinued due to an AE. Immune responses to Vaqta, PedvaxHIB, and Infanrix given concomitantly were non-inferior to nonconcomitant responses. Vaqta administered with PedvaxHIB & Infanrix had an acceptable safety profile in 15-month-old children.
Asunto(s)
Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Vacunas contra Haemophilus/inmunología , Vacunas contra la Hepatitis A/inmunología , Inmunogenicidad Vacunal/inmunología , Polisacáridos Bacterianos/inmunología , Vacunas Combinadas/efectos adversos , Vacunas Combinadas/inmunología , Anticuerpos Antibacterianos/sangre , Proteínas de la Membrana Bacteriana Externa/efectos adversos , Difteria/inmunología , Difteria/prevención & control , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/efectos adversos , Infecciones por Haemophilus/inmunología , Infecciones por Haemophilus/prevención & control , Vacunas contra Haemophilus/efectos adversos , Hepatitis A/inmunología , Hepatitis A/prevención & control , Vacunas contra la Hepatitis A/efectos adversos , Humanos , Lactante , Polisacáridos Bacterianos/efectos adversos , Tétanos/inmunología , Tétanos/prevención & control , Vacunas Conjugadas/efectos adversos , Vacunas Conjugadas/inmunología , Factores de Virulencia de Bordetella/inmunología , Tos Ferina/inmunología , Tos Ferina/prevención & controlRESUMEN
Lyme borreliosis (LB) patients who recover, as well as previously infected asymptomatic individuals, remain vulnerable to reinfection with Borrelia burgdorferi sensu lato. There is limited information available about the use of OspA vaccines in this population. In this study, a randomized double-blind phase I/II trial was performed to investigate the safety and immunogenicity of a novel multivalent OspA vaccine in healthy adults who were either seronegative or seropositive for previous B. burgdorferi sensu lato infection. The participants received three monthly priming immunizations with either 30 µg or 60 µg alum-adjuvanted OspA antigen and a booster vaccination either 6 months or 9 to 12 months after the first immunization. The antibody responses to the six OspA serotypes included in the vaccine were evaluated. Adverse events were predominantly mild and transient and were similar in the seronegative and seropositive populations. Substantial enzyme-linked immunosorbent assay (ELISA) and surface-binding antibody responses against all six OspA antigens were induced after the primary immunization schedule in both populations, and they were substantially increased with both booster schedules. The antibody responses induced by the two doses were similar in the seronegative population, but there was a significant dose response in the seropositive population. These data indicate that the novel multivalent OspA vaccine is well tolerated and immunogenic in individuals previously infected with B. burgdorferi sensu lato. (This study is registered at ClinicalTrials.gov under registration no. NCT01504347.).
Asunto(s)
Antígenos de Superficie/efectos adversos , Antígenos de Superficie/inmunología , Proteínas de la Membrana Bacteriana Externa/efectos adversos , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/efectos adversos , Vacunas Bacterianas/inmunología , Grupo Borrelia Burgdorferi/inmunología , Lipoproteínas/efectos adversos , Lipoproteínas/inmunología , Enfermedad de Lyme/inmunología , Enfermedad de Lyme/prevención & control , Vacunación/efectos adversos , Vacunación/métodos , Adyuvantes Inmunológicos/administración & dosificación , Adolescente , Adulto , Anciano , Compuestos de Alumbre/administración & dosificación , Anticuerpos Antibacterianos/sangre , Antígenos de Superficie/administración & dosificación , Proteínas de la Membrana Bacteriana Externa/administración & dosificación , Vacunas Bacterianas/administración & dosificación , Método Doble Ciego , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lipoproteínas/administración & dosificación , Masculino , Persona de Mediana Edad , Adulto JovenAsunto(s)
Adyuvantes Inmunológicos/efectos adversos , Antígenos de Superficie/efectos adversos , Antígenos de Superficie/inmunología , Proteínas de la Membrana Bacteriana Externa/efectos adversos , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/efectos adversos , Vacunas Bacterianas/inmunología , Borrelia burgdorferi/inmunología , Lipoproteínas/efectos adversos , Lipoproteínas/inmunología , Vacunas contra Enfermedad de Lyme/efectos adversos , Vacunas contra Enfermedad de Lyme/inmunología , Femenino , Humanos , MasculinoAsunto(s)
Adyuvantes Inmunológicos/efectos adversos , Antígenos de Superficie/efectos adversos , Antígenos de Superficie/inmunología , Proteínas de la Membrana Bacteriana Externa/efectos adversos , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/efectos adversos , Vacunas Bacterianas/inmunología , Borrelia burgdorferi/inmunología , Lipoproteínas/efectos adversos , Lipoproteínas/inmunología , Vacunas contra Enfermedad de Lyme/efectos adversos , Vacunas contra Enfermedad de Lyme/inmunología , Femenino , Humanos , MasculinoAsunto(s)
Adyuvantes Inmunológicos/efectos adversos , Antígenos de Superficie/efectos adversos , Antígenos de Superficie/inmunología , Proteínas de la Membrana Bacteriana Externa/efectos adversos , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/efectos adversos , Vacunas Bacterianas/inmunología , Borrelia burgdorferi/inmunología , Lipoproteínas/efectos adversos , Lipoproteínas/inmunología , Vacunas contra Enfermedad de Lyme/efectos adversos , Vacunas contra Enfermedad de Lyme/inmunología , Femenino , Humanos , MasculinoAsunto(s)
Antígenos de Superficie/administración & dosificación , Antígenos de Superficie/inmunología , Proteínas de la Membrana Bacteriana Externa/administración & dosificación , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/inmunología , Lipoproteínas/administración & dosificación , Lipoproteínas/inmunología , Enfermedad de Lyme/prevención & control , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/inmunología , Antígenos de Superficie/efectos adversos , Proteínas de la Membrana Bacteriana Externa/efectos adversos , Vacunas Bacterianas/efectos adversos , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Humanos , Lipoproteínas/efectos adversos , Enfermedad de Lyme/inmunologíaAsunto(s)
Aluminio/metabolismo , Proteínas de la Membrana Bacteriana Externa/efectos adversos , Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Vacunas contra Haemophilus/efectos adversos , Vacunas contra Hepatitis B/efectos adversos , Recien Nacido Prematuro , Vacunas Neumococicas/efectos adversos , Vacuna Antipolio de Virus Inactivados/efectos adversos , Polisacáridos Bacterianos/efectos adversos , Oligoelementos/metabolismo , Aluminio/sangre , Aluminio/orina , Biomarcadores/sangre , Biomarcadores/orina , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Espectrometría de Masas , Oligoelementos/sangre , Oligoelementos/orinaAsunto(s)
Adyuvantes Inmunológicos/efectos adversos , Antígenos de Superficie/efectos adversos , Antígenos de Superficie/inmunología , Proteínas de la Membrana Bacteriana Externa/efectos adversos , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/efectos adversos , Vacunas Bacterianas/inmunología , Borrelia burgdorferi/inmunología , Lipoproteínas/efectos adversos , Lipoproteínas/inmunología , Vacunas contra Enfermedad de Lyme/efectos adversos , Vacunas contra Enfermedad de Lyme/inmunología , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Lyme borreliosis is caused by Borrelia burgdorferi sensu stricto in the USA and by several Borrelia species in Europe and Asia, but no human vaccine is available. We investigated the safety and immunogenicity of adjuvanted and non-adjuvanted vaccines containing protective epitopes from Borrelia species outer surface protein A (OspA) serotypes in healthy adults. METHODS: Between March 1, 2011, and May 8, 2012, we did a double-blind, randomised, dose-escalation phase 1/2 study at four sites in Austria and Germany. Healthy adults aged 18-70 years who were seronegative for B. burgdorferi sensu lato were eligible for inclusion. Participants were recruited sequentially and randomly assigned to one of six study groups in equal ratios via an electronic data capture system. Participants and investigators were masked to group allocation. Participants received three vaccinations containing 30 µg, 60 µg, or 90 µg OspA antigen with or without an adjuvant, with intervals of 28 days, and a booster 9-12 months after the first immunisation. The coprimary endpoints were the frequency and severity of injection-site and systemic reactions within 7 days of each vaccination, and the antibody responses to OspA serotypes 1-6, as established by ELISA. This study is registered with ClinicalTrials.gov, number NCT01504347. FINDINGS: 300 participants were randomly assigned: 151 to adjuvanted vaccines (50 to 30 µg, 51 to 60 µg, and 50 to 90 µg doses), and 149 to non-adjuvanted vaccines (50 to 30 µg, 49 to 60 µg, and 50 to 90 µg doses). Adverse reactions were predominantly mild, and no vaccine-related serious adverse events were reported. The risk of systemic reactions (risk ratio 0·54 [95% CI 0·41-0·70]; p<0·0001) and of moderate or severe systemic reactions (0·35 [0·13-0·92]; p=0·034) was significantly lower for adjuvanted than non-adjuvanted formulations. The 30 µg adjuvanted formulation had the best tolerability profile; only headache (five [10%, 95% CI 4-20] of 50), injection-site pain (16 [32%, 21-45]), and tenderness (17 [34%, 23-47]) affected more than 6% of patients. All doses and formulations induced substantial mean IgG antibody titres against OspA serotypes 1-6 after the first three vaccinations (range 6944-17,321) and booster (19,056-32,824) immunisations. The 30 µg adjuvanted formulation induced the highest antibody titres after the booster: range 26,143 (95% CI 18,906-36,151) to 42,381 (31,288-57,407). INTERPRETATION: The novel multivalent OspA vaccine could be an effective intervention for prevention of Lyme borreliosis in Europe and the USA, and possibly worldwide. Larger confirmatory formulation studies will need to be done that include individuals seropositive for Borrelia burgdorferi sensu lato before placebo-controlled phase 3 efficacy studies can begin. FUNDING: Baxter.
Asunto(s)
Adyuvantes Inmunológicos/efectos adversos , Antígenos de Superficie/efectos adversos , Antígenos de Superficie/inmunología , Proteínas de la Membrana Bacteriana Externa/efectos adversos , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/efectos adversos , Vacunas Bacterianas/inmunología , Borrelia burgdorferi/inmunología , Lipoproteínas/efectos adversos , Lipoproteínas/inmunología , Vacunas contra Enfermedad de Lyme/efectos adversos , Vacunas contra Enfermedad de Lyme/inmunología , Adulto , Método Doble Ciego , Femenino , Cefalea/inducido químicamente , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Dolor/inducido químicamente , Adulto JovenAsunto(s)
Antígenos de Superficie/efectos adversos , Antígenos de Superficie/inmunología , Proteínas de la Membrana Bacteriana Externa/efectos adversos , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/efectos adversos , Vacunas Bacterianas/inmunología , Lipoproteínas/efectos adversos , Lipoproteínas/inmunología , Enfermedad de Lyme/epidemiología , Enfermedad de Lyme/prevención & control , Antígenos de Superficie/administración & dosificación , Proteínas de la Membrana Bacteriana Externa/administración & dosificación , Vacunas Bacterianas/administración & dosificación , Ensayos Clínicos Fase III como Asunto , Humanos , Lipoproteínas/administración & dosificación , Enfermedad de Lyme/inmunología , Estados Unidos/epidemiologíaRESUMEN
The trend of increased survival in advanced tumors suggests the possibility of the transformation of cancer into a chronic disease. That goal will require therapeutic weapons with low toxicity that can be used chronically. Here we summarize the development of a therapeutic vaccine consisting in recombinant EGF chemically linked to a protein from Neisseria meningitides. In mice, the vaccine elicited antibodies to self-EGF and had anti-tumor activity. Clinical trials have shown that the vaccine is also immunogenic and well tolerated in humans. The vaccination produced a decrease in plasma EGF concentration. Advanced lung cancer patients eliciting high antibody titers of EGF had better survival. The vaccine can be used long term and integrated with other treatment modalities.
Asunto(s)
Proteínas de la Membrana Bacteriana Externa/uso terapéutico , Vacunas contra el Cáncer/uso terapéutico , Factor de Crecimiento Epidérmico/uso terapéutico , Neoplasias Pulmonares/terapia , Neisseria meningitidis/inmunología , Animales , Autoanticuerpos/sangre , Proteínas de la Membrana Bacteriana Externa/efectos adversos , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas contra el Cáncer/efectos adversos , Enfermedad Crónica , Factor de Crecimiento Epidérmico/efectos adversos , Factor de Crecimiento Epidérmico/sangre , Factor de Crecimiento Epidérmico/inmunología , Humanos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Resultado del Tratamiento , Vacunas Sintéticas/uso terapéuticoRESUMEN
A wide range of neurological complications have been reported via the medical literature and the VAERS system after vaccination with recombinant outer surface protein A (OspA) of Borrelia. To explore this issue, 24 patients reporting neurological adverse events (AE) after vaccination with Lymerix, out of a group of 94 patients reporting adverse events after Lymerix vaccination, were examined for causation. Five reports of cerebral ischemia, two transient Ischemic attacks, five demyelinating events, two optic neuritis, two reports of transverse myelitis, and one non-specific demyelinating condition are evaluated in this paper. Caution is raised on not actively looking for neurologic AE, and for not considering causation when the incidence rate is too low to raise a calculable difference to natural occurence.
Asunto(s)
Antígenos de Superficie/efectos adversos , Proteínas de la Membrana Bacteriana Externa/efectos adversos , Vacunas Bacterianas/efectos adversos , Borrelia burgdorferi/inmunología , Lipoproteínas/efectos adversos , Enfermedad de Lyme/prevención & control , Sistema Nervioso/efectos de los fármacos , Vacunación/efectos adversos , Sistemas de Registro de Reacción Adversa a Medicamentos , Antígenos de Superficie/administración & dosificación , Proteínas de la Membrana Bacteriana Externa/administración & dosificación , Vacunas Bacterianas/administración & dosificación , Isquemia Encefálica/etiología , Enfermedades Desmielinizantes/etiología , Femenino , Humanos , Lipoproteínas/administración & dosificación , Enfermedad de Lyme/epidemiología , Masculino , Persona de Mediana Edad , Neuritis Óptica/etiología , Medición de Riesgo , Estados Unidos/epidemiología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/efectos adversosRESUMEN
OBJECTIVE: There are few recent population-based assessments of vaccine coverage in premature infants available. This study assesses and compares age- and dose-specific immunization coverage in children of different birth weight categories during the first year of life. METHODS: We performed a retrospective cohort analysis of computerized vaccination data from a large managed care organization in southern California. The participants were children born between January 1, 1997, and December 31, 2002, and continuously enrolled from birth to at least 12 months of age in the Southern California Kaiser Permanente health plan. We measured age-specific up-to-date and age-appropriate immunization rates according to birth weight (extremely low birth weight: <1000 g; very low birth weight: 1000-1499 g; low birth weight: 1500-2499 g; normal birth weight: >/=2500 g) for 4 vaccines (hepatitis B, diphtheria and tetanus toxoids with pertussis, Haemophilus influenzae type b, and poliovirus) through the first year of life. RESULTS: We identified 127 833 infants born during the study period and continuously enrolled through the first year of life; 120 048 were normal birth weight infants; 6491 were low birth weight infants; 788 were very low birth weight infants; and 506 were extremely low birth weight infants. Vaccine-specific age-appropriate immunization rates were 3% to 15% lower for low birth weight infants and 17% to 33% lower for extremely low birth weight infants compared with the rates for normal birth weight infants in the first 6 months of life. Extremely low birth weight infants had the lowest age-specific up-to-date immunization levels (5%-31% lower) compared with normal birth weight infants at each age assessed. By 12 months, extremely low birth weight infants still had significantly lower up-to-date levels (87%) compared with very low birth weight, low birth weight, and normal birth weight infants (91%-92%). CONCLUSIONS: Despite recommendations that lower birth weight infants be vaccinated as the same chronological age as normal birth weight infants, extremely low birth weight and very low birth weight infants are immunized at significantly lower rates relative to low birth weight and normal birth weight infants at 2, 4, and 6 months of age. However, by 12 months of age this finding persists only in extremely low birth weight infants.
Asunto(s)
Recien Nacido con Peso al Nacer Extremadamente Bajo , Recién Nacido de Bajo Peso , Enfermedades del Prematuro/epidemiología , Recién Nacido de muy Bajo Peso , Programas Controlados de Atención en Salud/estadística & datos numéricos , Vacunación/estadística & datos numéricos , Factores de Edad , Proteínas de la Membrana Bacteriana Externa/administración & dosificación , Proteínas de la Membrana Bacteriana Externa/efectos adversos , California , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/efectos adversos , Femenino , Vacunas contra Haemophilus/administración & dosificación , Vacunas contra Haemophilus/efectos adversos , Humanos , Esquemas de Inmunización , Lactante , Recién Nacido , Masculino , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Vacuna Antipolio de Virus Inactivados/efectos adversos , Polisacáridos Bacterianos/administración & dosificación , Polisacáridos Bacterianos/efectos adversos , Estudios RetrospectivosRESUMEN
OBJECTIVE: To evaluate the Immunogenicity of Group A and Group C Meningococcal conjugate Vaccine with coupling Group B Meningococcal Outer Membrane Protein (Men B-OMP). METHODS: 458 healthy children aged 3-5 months, 6-23 months, 2-6 years and 7-24 years were given the Groups A and C conjugate Vaccine with MenB-OMP or other vaccine as control group to measure the pre-and post-vaccination Men A and C and B by Serum Bactericidal Assay (SBA) in the double-blind randomized controlled trial. RESULTS: 97.65%-100% were 4 times or greater increase in SBA titer for the healthy children given the Groups A and C conjugate Vaccine with MenB-OMP, The geometric mean titer of SBA were 1:194-1:420, which significantly higber than controls. CONCLUSION: The Group A and C conjugate Vaccine with MenB-OMP was safe and well immunogenic.
Asunto(s)
Proteínas de la Membrana Bacteriana Externa/inmunología , Meningitis Meningocócica/inmunología , Vacunas Meningococicas/inmunología , Adolescente , Proteínas de la Membrana Bacteriana Externa/administración & dosificación , Proteínas de la Membrana Bacteriana Externa/efectos adversos , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Meningitis Meningocócica/microbiología , Vacunas Meningococicas/administración & dosificación , Vacunas Meningococicas/efectos adversos , Neisseria meningitidis Serogrupo A/inmunología , Neisseria meningitidis Serogrupo B/inmunología , Neisseria meningitidis Serogrupo C/inmunología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/efectos adversos , Vacunas Conjugadas/inmunología , Adulto JovenRESUMEN
The incidence of invasive diseases, including meningitis caused by Haemophilus influenzae type b (Hib) was markedly decreased after routine immunization of Hib vaccine through diverse schedules in many countries. The purpose of this study was to evaluate the immunogenicity and safety of Hib conjugate vaccines in Korean children before the implementation of a national immunization program against Hib in Korea. A multicenter controlled trial was performed on two different Hib vaccines in Korean children. A total of 319 infants were enrolled: 199 infants were immunized with the Hib polysaccharide conjugated to the tetanus toxoid (PRP-T) and 120 infants with the Hib polysaccharide conjugated to the outer-membrane protein of Neisseria meningitides (PRP-OMP). Immunogenicity was evaluated by enzyme-linked immunosorbent assay (ELISA) and serum bactericidal assay. Both vaccines showed good immunologic responses after primary immunization. After 2 doses of PRP-T or PRP-OMP, 78.9% and 91.7% of infants achieved an antibody level of >or=1.0 microg/mL, respectively. Both vaccines were safe and well-tolerated. No serious adverse events were observed. Thus, Hib conjugate vaccines appear to be safe and show good immunogenicity in Korean infants. These results will be important reference data for the implementation of Hib vaccine in the national immunization program of Korea.
Asunto(s)
Proteínas de la Membrana Bacteriana Externa/efectos adversos , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas contra Haemophilus/efectos adversos , Vacunas contra Haemophilus/inmunología , Haemophilus influenzae tipo b/inmunología , Polisacáridos Bacterianos/efectos adversos , Polisacáridos Bacterianos/inmunología , Toxoide Tetánico/efectos adversos , Toxoide Tetánico/inmunología , Proteínas de la Membrana Bacteriana Externa/administración & dosificación , Ensayo de Inmunoadsorción Enzimática , Vacunas contra Haemophilus/administración & dosificación , Humanos , Lactante , Corea (Geográfico) , Polisacáridos Bacterianos/administración & dosificación , Toxoide Tetánico/administración & dosificaciónRESUMEN
Throughout the history of vaccination, vaccines have been accused of harmful side effects. Adverse events following immunization may be caused by the active antigen in the vaccine or other constituents, such as adjuvants, or may merely be coincidental. Possible neurological side effects have always obtained high attention. However, the risk of serious events caused by existing vaccines or aluminum adjuvants is very small. Currently, there are several new vaccines and adjuvants in the pipeline. Of these vaccines, many will be offered mainly to adolescents or adults. When taken into general use, some of them will probably be associated with serious adverse events. Although coincidence will be the most probable explanation in most cases, causality will have to be discussed in many situations. Preparing to address the causes of these adverse events is important.
Asunto(s)
Adyuvantes Inmunológicos/efectos adversos , Compuestos de Aluminio/efectos adversos , Proteínas de la Membrana Bacteriana Externa/efectos adversos , Vacunas Meningococicas/efectos adversos , Neisseria meningitidis Serogrupo B/inmunología , Enfermedades del Sistema Nervioso/inducido químicamente , Animales , Humanos , Infecciones Meningocócicas/prevención & control , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/epidemiologíaRESUMEN
The host innate immune defense protein lipocalin 2 binds bacterial enterobactin siderophores to limit bacterial iron acquisition. To counteract this host defense mechanism bacteria have acquired the iroA gene cluster, which encodes enzymatic machinery and transporters that revitalize enterobactin in the form of salmochelin. The iroB enzyme introduces glucosyl residues at the C5 site on 2,3-dihydroxybenzoylserine moieties of enterobactin and thereby prevents lipocalin 2 binding. Additional strategies to evade lipocalin 2 have evolved in other bacteria, such as Mycobacteria tuberculosis and Bacillus anthracis. Targeting these specialized bacterial evasion strategy may provide a mechanism to reinvigorate lipocalin 2 in defense against specific pathogens.
Asunto(s)
Proteínas de Fase Aguda/fisiología , Proteínas de la Membrana Bacteriana Externa/genética , Interacciones Huésped-Patógeno/genética , Hierro/metabolismo , Lipocalinas/fisiología , Proteínas Proto-Oncogénicas/fisiología , Proteínas de Fase Aguda/genética , Animales , Proteínas de la Membrana Bacteriana Externa/efectos adversos , Proteínas de la Membrana Bacteriana Externa/antagonistas & inhibidores , Proteínas de la Membrana Bacteriana Externa/fisiología , Diseño de Fármacos , Enterobactina/análogos & derivados , Enterobactina/fisiología , Marcación de Gen , Glucósidos , Interacciones Huésped-Patógeno/fisiología , Humanos , Lipocalina 2 , Lipocalinas/genética , Modelos Biológicos , Familia de Multigenes/fisiología , Proteínas Proto-Oncogénicas/genéticaAsunto(s)
Proteínas de la Membrana Bacteriana Externa/efectos adversos , Infecciones Meningocócicas/prevención & control , Vacunas Meningococicas/efectos adversos , Neisseria meningitidis Serogrupo B/inmunología , Proteínas de la Membrana Bacteriana Externa/administración & dosificación , Proteínas de la Membrana Bacteriana Externa/inmunología , Ensayos Clínicos como Asunto , Humanos , Infecciones Meningocócicas/microbiología , Vacunas Meningococicas/administración & dosificación , Vacunas Meningococicas/inmunologíaRESUMEN
BACKGROUND: Concerns of immune cross-reactivity, between epitopes of the group A streptococcal (GAS) M-proteins and host proteins have hindered the progress of an effective GAS vaccine. An ideal M-protein based subunit vaccine should not elicit heart tissue cross-reactive antibody responses and should not activate M-protein specific CD4+ T-cells. In the current study we used a bioinformatic and immunoinformatic approach to assess the safety of J8 and J14, chimeric vaccine constructs containing a GAS derived M-protein epitope embedded in flanking GCN4 region. We demonstrate that at the primary amino acid level J8 and J14 show very little homology to human proteins. ProPred, RANKPEP and HLABIND algorithms failed to predict significant binding between the M-protein specific regions of J8 and J14 and class II binding alleles. A single peptide was predicted to bind to HLA class I allele B_2705. This data was supported by cellular proliferation assays demonstrating few peripheral blood mononuclear cells (PBMCs) from donors respond to J8 and J14. Reassuringly, there was no correlation between proliferation to these peptides, and proliferation to host proteins. This data suggests that J8 and J14 are unlikely to induce cross-reactive immune responses, and will be safe for use in humans.